غذایی رژیم مکملهایDietary Supplements

By : Somayyeh Nasiripour,pharm.D-Ph.D.Assistant professor at IUMS

Assistant professor at IUMS

تعریف آمريكا در

يا يك حاوي كه شود مي اطالق محصولي به غذايي مكملمثل ويژه غذايي ماده چند

آمينه اسيدهاي گياهي، معدني، مواد ها، ساير ويتامين يابوده مواد

صورت به وشده مصرف دهان راه از مايع يا كپسول قرص،

باعنوان برچسب و dietary supplement

. باشد داشته

2

Supplement Use

• Use of any dietary supplements: 50% of Americans (aged ≥ 1 year)

• Regular use of multivitamin–multimineral (MVM) supplements: 30% to 40% of Americans

• Nearly 16% of prescription drug users also report having taken a dietary supplement at the same time

میزان مصرف مکملها در ایران 2010در مطالعه ای در ایران که در سال •

فرد بالغ در 1004منتشر شده است، از میان غرب تهران :

افراد طی یکسال گذشته مکمل مولتی 42%–ویتامین، مکمل مینرال یا مکمل حاوی هر دو

استفاده کرده بودند Omega-3 fatty acids % از مکملهای حاوی4/9–

or fish oilاستفاده کرده بودند IRANIAN JOURNAL OF ENDOCRINOLOGY AND METABOLISM (IJEM) NOVEMBER 2010; 12(4 (SN 52)):375-365.

تا 2010در مطالعه ای که از اواخر سال • در استان گیالن انجام 2011اواسط سال

گردید مصرف مکملهای غیر گیاهی بررسی شد:

مرد بالغ676 زن و 1425از میان •میزان مصرف یکی از مکملهای آهن، کلسیم، •

مولتی ویتامین/مولتی مینرال و روغن ماهی%20در آقایان •%48/4در خانمها •

Mediterranean Journal of Nutrition and Metabolism . April 2013, Volume 6, Issue 1, pp 69-72

میزان مصرف مکملها در ایران

o 29000تخمین زده می شود که حدود نوع مکمل غذائی در بازار دنیا وجود دارد و

محصول جدید هم به 1000در هر سال بازار عرضه می شود.

o علت اساسی گسترش تولید این محصوالت = سودآوری بی نظیر آنها

o امروزه در دنیا، صنعت تولید مکمل ها را به عنوان صنایع بیلیون دالری می شناسند

موارد مصرف مکملهای رژیم غذایی بر اساس مستندات

علمیافرادی که رژیم غذایی کم کالری دارند ) •

کالری در روز(1600کمتر از کسانیکه به رژیم گیاهخواری کامل •

پایبندندخانمهای باردار یا در سنین باروری•سالمندانی که دریافت کافی از رژیم •

غذایی ندارندافرادی که به دلیل شرایط پزشکی و •

بیماری، انتخابهای غذایی محدودی دارند

Why Americans Used MVM?

• Decrease disease risk

• Compensate for perceived nutritional

deficiencies

• Provide energy

• Adhere to physician recommendations

• Promote general health

مطالعه ای ملی در ایاالت متحده آمریکا نشان داد:•در بیشتر موارد مصرف کنندگان در مورد جایگاه، علت، شرایط –

و احتیاطات مصرف مکملها با پزشک یا داروساز خود صحبت نمی کنند.

دالیل روآوردن مردم به مصرف مکمل ها و خود درمانی با آنها:•این فراورده ها بدون نیاز به نسخه در دسترس مردم است – این تصور که فرآورده های طبیعی ایمن و بی خطر هستند ) در –

مورد مکمل های با منشا طبیعی و گیاهی (تبلیغات گسترده–

Nutrition Survey in older children (>4)

1.5% of boys and 5% of girls were

anaemic 13% and 27% were mildly iron deficient 10% of boys and 20% of girls a poor

intake of zinc Vitamin A deficiency were 10% and 11% For magnesium the respective figures

were 12% and 27%

Why we use dietary supplements?

05/01/2023

10

• Distinguished from Drugs:• Drugs are intended to diagnose, cure,

mitigate, treat, or prevent disease• Both intended to affect structure and function

of body• Drug must undergo FDA approval after

clinical studies to determine effectiveness and safety

• D/S no pre-market testing

مکملهای ژریم غذایی : دارو یا غذا؟

• Distinguished from Foods:– Foods not intended to affect structure

and function of body.

– D/S intended only to supplement diet: • Not represented for use as

conventional food• Not intended as sole item of a meal

or the diet”

مکملهای ژریم غذایی : دارو یا غذا؟

مکملهای ژریم غذایی : دارو یا غذا؟

مکمل های غذایی:از راه دستگاه گوارش مص�رف می شوند •

شکل خوراکی : کپسول، قرص، شربت، پودر، گرانول، سافت ژل، آمپول –خوراکی، قطره، ورقه های خوراکی

به عنوان یک غذای معمولی و یا یک وعده غذایی تنها به کار •نمی روند

ویتامین ها ، مواد معدنی، گیاهان، اسیدهای آمینه، قندها، •چربیها، آنزیم ها، پروبیوتیک ها، یک ماده تغلیظ شده،

متابولیت، مواد تکمیل کننده و یا عصارهدارای فرموالسیون خاص و ثابت قابل اندازه گیری •جهت کاربرد د�ر انسان به منظور تکمیل نیاز تغذیه ای، •

افزایش د�ریافت تغذیه ای و یا ایجاد یک اثر فیزیولوژیک می باشند

مکملهای ژریم غذایی : دارو یا غذا؟

فقدان و یا کمبود یک یا چند ماده مغذی اولیه در •رژیم غذایی را تکمیل می نمایند

و از طریق ارتقاء عملکرد و یا پیشگیری از •

اختالالت دستگاههای مختلف بدن موجبات افزایش سالمت را فراهم می کنند

ضمناً هیچگونه ادعای تشخیصی، پیشگیری و یا •درمانی از یک بیماری خاص را ندارند

Dietary Supplement Label

Serving Size

دستور مصرف محصول به صورت روزانه مي •باشد

( (: در مورد مکمل ها Serving sizeاندازه واحدها • عدد در روز متغیر است1 – 3از

این موضوع در قضاوت در مورد میزان مواد •موثره و ماده مغذی و نیز از بعد اقتصادی باید

لحاظ شود.

Dietary reference intakes (DRIs) represent four concepts

• Recommended Dietary Allowance • average daily intake that is sufficient to meet the

dietary requirement of nearly all healthy peopleRDA• Adequate Intake• is used when the RDA cannot be determined AI• Estimated Average Requirement EAR• Tolerable Upper Level• maximum daily intake of a nutrient that is likely to

pose no risk of adverse effectsUL

Daily Value

• The Percent Daily Value on the Nutrit containing 60 mg vitamin C is considered to provide 100% of the daily value

• If the label lists 15 percent for calcium, it means that one serving provides 15 percent of the calcium you need each day

خصوصیات برچسب مکمل ها بر اساس

قوانین ایرانارائه اطالعات بر چسب به زبان •

فارسی

درج جمله "این محصول برای •تشخیص، پیشگیری و یا درمان

بیماری نمی باشد"

درج شماره پروانه

بهداشتی و IRC

تعداد و شکل

فرآورده

طریقه مصرف توصیه

شده

درج عبارت" مکمل رژیمی غذایی"

تاریخ تولید و انقضا ء

میزان مصرف

شرایط نگهدار

ی

موارد منع

مصرف و

هشدارها

نام وآدرس و شماره تماس شرکت

وارد کننده

موارد مصرف

Vitamin supplementation

in disease prevention

— Vitamins

• vitamins (with the exception of vitamin D) cannot be synthesized by humans, they need to be ingested in the diet to prevent disorders of metabolism

• Pregnancy and alcohol consumption may increase requirements for some vitamins.

Testing

• — Measurement of serum levels of several vitamins is widely available

• Inadequate intake or low serum levels of some vitamins can be associated with biochemical abnormalities.

• As examples, the serum concentration of homocysteine rises with diets low in folic acid, methylmalonic acid rises with low intake of vitamin B12, and parathyroid hormone rises with low intake of vitamin D

• improve with increasing intake

FOLIC ACID • Folate is the natural form of the vitamin found

in food and is present in green, leafy vegetables, fruits, cereals, grains, nuts, and meats.

• Folic acid is the synthetic form of the vitamin that is included in supplements and food fortification, has many of the same biologic effects as folate, but is more bioavailable and therefore more effective dose for dose

• Overall, the only well-established benefit of folic acid supplementation is the prevention of neural tube defects because folate is required for normal cell division

Flate in Cancer• Biologic and observational evidence suggest that sufficient folate intake

might prevent cancers in certain populations at risk as Folate deficiency may contribute to aberrant DNA synthesis and carcinogenesis

• In a 2013 meta-analysis of randomized trials of folic acid in patients with colorectal adenoma (3 trials; n = 2652) or for prevention of cardiovascular disease (10 trials; n = 46,969), during an average of 5.2 years of treatment, there was no significant difference in overall cancer incidence for patients assigned to folic acid or placebo (7.7 versus 7.3 percent; RR 1.06, 95% CI 0.99-1.13)

• One limitation of the included trials is that the average duration of intervention (five years) is short and may not be sufficient to characterize long-term benefits or harm of folic acid supplementation. In addition, the trials do not address underlying nutrition status and other preventive measures.

Since the evidence is inconclusive, we recommend not taking folic acid supplementation for the sole purpose of reducing cancer risk.

Folic acid in Cardiovascular disease • High levels of homocysteine are associated with

an increased risk of cardiovascular disease.• Supplementation with folic acid, vitamin B6, and

vitamin B12 can lower homocysteine levels.• However, meta-analyses of randomized trials of

supplementation for secondary prevention do not support the hypothesis that these vitamins prevent cardiovascular disease

Folic aci & risk of hypertension

• High folate intake may reduce the risk of hypertension.

• Still There is insufficient evidence to recommend folic acid supplementation to reduce the risk of hypertension

Folic aci & hearing loss .• There is conflicting observational evidence

about whether increased serum folate levels are associated with a decreased risk of age-related hearing loss

• Calcium/vitamin D

•first step in the prevention or treatment of osteoporosis is ensuring adequate nutrition, particularly maintaining an adequate intake of calcium and vitamin D

•Vitamin D enhances intestinal absorption of calcium and phosphate. Low concentrations of vitamin D are associated with impaired calcium absorption, a negative calcium balance, and a compensatory rise in parathyroid hormone, which results in excessive bone resorption.

•calcium and vitamin D alone are insufficient to prevent bone loss

OPTIMAL INTAKE

postmenopausal women •1200 mg of calcium (total of diet and supplement) and 800 int. units of vitamin D daily with osteoporosis

premenopausal women or in men with osteoporosis •1000 mg of calcium (total of diet and supplement) and 600 int. units of vitamin D

We recommend not administering yearly high-dose (eg, 500,000 units) vitamin D.

total intake of calcium (diet plus supplements) should not routinely exceed 2000 mg/day

•Optimal intake can be achieved with a combination of diet plus supplements

•prefer that as much as possible (at least half) of the calcium come from dietary sources.

•supplements are not less effective than calcium found naturally in dairy products. However, supplements may have more adverse effects, particularly kidney stones.

Calcium •cheapest and therefore often a good first choice•absorption is better when taken with meals•poorly absorbed in patients taking proton pump inhibitors or H2 blockers•calcium carbonate is 40 percent elemental calcium, so that 1250 mg of calcium carbonate contains 500 mg of elemental calcium

Calcium carbonate

•, calcium citrate is well absorbed in the fasting state, and equally absorbed compared with calcium carbonate taken with a meal•patients taking PPI or H2 blockers, calcium citrate is a first line calciumcalcium

citratesupplementation in excess of 500 mg/day should be given in divided doses

labeling reports the amount per “serving” instead of the amount per tablet, it is important to verify that the patient is taking the correct number of tablets per serving

Nephrolithiasis

• Ingested calcium is absorbed in the intestines and later excreted in the urine

• Although this suggests that a diet high in calcium might promote stone disease, the opposite effect is seen as the risk of stone formation appears to be reduced in both men and women.

• In contrast, calcium supplements may slightly increase the propensity to form stones, at least in older women

• In the Nurses' Health Study, a higher dietary calcium intake was associated with a lower incidence of stone disease (multivariate relative risk 0.65 for highest versus lowest quintile of calcium intake) while calcium supplements were associated with a small increase in risk (relative risk 1.2 in supplement users compared with nonusers)

Cardiovascular disease • risk of cardiovascular disease (CVD) is controversial • There may be benefits of calcium supplementation on risk factors, such as a

reduction in weight, blood pressure, and in serum cholesterol concentrations (of about 5 percent) in patients with mild to moderate hypercholesterolemia.

• in one study After seven years, calcium plus vitamin D supplementation had no significant effect on the incidence of myocardial infarction

• However, the findings of two meta-analyses evaluating calcium or calcium with or without vitamin D supplementation (eight and nine trials, respectively) raised some concern about an increased risk of myocardial infarction (MI) in patients randomly assigned to calcium versus placebo (

• In contrast to the findings with calcium supplements, prospective cohort studies showed either no relationship or an inverse relationship between dietary calcium intake and risk of heart disease death or MI

Vit D

• Thus, all adults who do not have regular effective sun exposure year round should consume at least 600 to 800 international units (units) of vitamin D3 (cholecalciferol) daily

slightly higher dose of vitamin D supplementation (at least 1000 and 800 to 1000 int. units daily, respectively) to older adults (≥65 years) to reduce the risk of fractures and falls

DEFINING VITAMIN D SUFFICIENCY

• UpToDate editors, favor maintaining the serum 25(OH)D concentration between 20 and 40 ng/mL (50 to 100 nmol/L), whereas other experts, including other UpToDate editors and the author of this topic, favor maintaining 25(OH)D levels between 30 and 50 ng/mL

• Experts agree that levels lower than 20 ng/mL are suboptimal for skeletal health

• minimum level of 30 ng/mL (75 nmol/L) is necessary in older adults to minimize the risk of falls and fracture

concerns were based upon the increase in fracture in patients treated with high dose vitamin D and conflicting studies describing a potential increased risk for some cancers (eg, pancreatic, prostate) and mortality with levels above 30 to 48 ng/mL

D insufficiency appears to be common

Dark skinned

Obese

Taking medications that accelerate the metabolism of vitamin D (such as phenytoin

Hospitalized on a general medical service &Institutionalized

Limited effective sun exposure due to protective clothing or consistent use of sun screens• Osteoporosis

Malabsorption, including inflammatory bowel disease and celiac disease

(IOM) has defined the upper limit for vitamin D as 4000 units daily for healthy

adults

Pregnancy • The optimal serum 25(OH)D level in pregnancy is unknown, but should be

at least 20 ng/mL• report suggesting a recommended daily allowance of 600 int

• In pregnant women with vitamin D deficiency, the safety of 50,000 int. units of vitamin D weekly for six to eight weeks has not been adequately studied,

• so some UpToDate editors treat vitamin D deficient and insufficient pregnant women more slowly by giving a total of 600 to 800 int. units of vitamin D3 daily. For pregnant women with vitamin D deficiency, other UpToDate editors agree with ACOG and the Endocrine Society that 1000 to 2000 int

The role of Vit D 3

•Physiologic doses of vitamin D attenuate bone loss and may decrease fracture rate. Osteoporosis

•randomized trials showing a reduction in risk of falls (relative risk reduction as high as 20 percent) following vitamin D supplementation, particularly when the baseline vitamin D status is poor Falls

•biologic reasons why vitamin D may protect against cancer, evidence for this effect in humans is mixed and expert groups have not recommended vitamin D supplements for the specific purpose of preventing cancer• Cancer

All-cause mortality

• Thus, although some data suggest an association between vitamin D deficiency and cancer, the direction of the association may depend upon the serum 25OHD concentration.

• The current evidence is insufficient to support large dose vitamin D supplementation for cancer prevention or treatment.

Other unproven effect of vit D3• n a review of four interventional randomized trials and a meta-analysis of six

trials, however, there was no effect of supplementation on cardiovascular outcomes, including myocardial infarction and stroke [ 66,72 ]. The meta-analysis also did not show a significant effect of vitamin D supplementation on cardiovascular risk factors (lipids, glucose, blood pressure)

CARDIOVASCULAR DISEASES AND HYPERTENSION

• In a meta-analysis of eight trials evaluating the effect of vitamin D supplementation on glycemia, there was no effect of supplementation on glycemia or incident diabetes [ 66 ]. However, a subsequent trial in severely vitamin D deficient Asians living in New Zealand revealed a modest improvement of their insulin sensitivity after six months of vitamin D supplementation

DIABETES AND METABOLIC SYNDROME

•In one trial, 243 patients with depression and low serum 25-hydroxyvitamin D levels (mean 19 ng/mL [47 nmol/L]) were randomly assigned to vitamin D supplementation (40,000 int. units weekly) or placebo [ 95 ]. After six months, there were no differences in depressive symptom scores

NEUROPSYCHIATRIC

FUNCTION

• Vitamin D– Reducing fracture risk in Osteoporosis

• In postmenopausal women: vitamin D 800 IU + calcium 1200 mg daily

• In premenopausal women and men: vitamin D 400 to 600 IU + calcium 1000 mg daily

– Falls• Vitamin D supplementation (700 to 1000 Units/day)

reduces the risk of falls in elderly

– Cancer: Not recommended– Infectious diseases: Not recommended– Autoimmune diseases: Not recommended– Cardiovascular diseases: Not recommended

Vitamin supplementation in disease prevention

ANTIOXIDANT

VITAMINS

vitamin A,

Vitamin c

Vitamin E

systematic review and meta-analysis of randomized trials of antioxidant supplements for the prevention of

gastrointestinal cancers found no decreased risk with supplementation

vitamin A consists of

• mostly found in animal sources of food• the form supplied by most supplements• Source: liver, kidney, egg yolk, and butter• absorption and storage of preformed vitamin A

(eg, in animal liver or dietary supplements) is efficient, and toxicity can occur if excessive quantities are ingested.

preformed vitamin A (retinol)

• found in plants• There are many forms of provitamin A, but beta-

carotene is only one that is metabolized by mammals into vitamin A.

• Source: in green leafy vegetables, sweet potato and carrots

• metabolism of provitamin A (beta-carotene) into active vitamin A is a highly regulated step, so excessive intake of vitamin A from plant sources is very unlikely to cause toxicity

provitamin A carotenoids

(beta-carotene and

others)

DEFICIENCY • it is still the third most common nutritional deficiency in the

world

• night blindness, complete blindness, and advanced stages of xerophthalmia occur in many malnourished children and adults

• ) • xerophthalmia can also be seen in resource-rich countries in

patients with disorders associated with fat malabsorption, such as cystic fibrosis, celiac disease, cholestatic liver disease such as primary biliary cholangitis, small bowel Crohn disease, and pancreatic insufficiency

diagnosis of vitamin A deficiency

serum retinol levels (levels less than 20 micrograms/dL

the ratio of retinol:RBP (a molar ratio <0.8

Clinical manifestations

Xerophthalmia

Poor bone growth

Impairment of the humoral and cell mediated immune

system via direct and indirect effects on the phagocytes

and T cells

Periodic supplementation is recommended for populations endemic for vitamin A deficiency, at the

following doses (where 1 microgram retinol = 3.3 international units)

supplements should be provided as frequent small doses not exceeding 10,000 international units daily or 25,000 international units, given weekly for a

minimum of 12 weeks during pregnancy until delivery

chronic ingestion of large amounts of synthetic (or "preformed") vitamin A (about 10 times higher than the

Recommended Dietary Allowance (RDA), or about 50,000 international units )

metabolism of provitamin A (beta-carotene, from plant sources) is highly regulated, so excessive ingestion of this

form of vitamin A is very unlikely to cause toxicity.

As an example, individuals who ingest large amounts of provitamin A (from plant sources) may develop yellow-tinged skin (carotenemia) without developing vitamin A

toxicity

Treatment of vitamin A toxicity consists of stopping vitamin A supplements and restricting vitamin A-rich foods (especially sources of pre-formed vitamin A, such as liver, kidney and egg

yolk).

Benefit of vit A

Cancer

Diets rich in beta carotene appear to be associated with lower risks of cancer. However, clinical trials of beta carotene supplementation have not confirmed a beneficial effect, and some suggest that beta carotene supplements may modestly increase the risk for lung cancer, but not other cancers.

Another study showed an increase in both prostate cancer incidence and mortality (23 and 15 percent, respectively) among subjects randomized to β-carotene [41]. The excess risk appeared to resolve over time once supplements were stopped

There is currently no strong evidence that vitamin A and

carotenoid supplements reduce the risk of cancer.

Cardiovascular disease

Randomized trials of vitamin A and β-carotene have shown no benefit for primary or secondary prevention of coronary heart disease (CHD)

Immunity

Vitamin A improves immunity in children living in developing countries where dietary intake is inadequate and life-threatening infectious diseases are common

Fractures

Women in the highest quintile of total vitamin A intake had a relative risk for hip fracture of 1.48 compared with women in the lowest quintile.

Thus, patients should be cautioned against diets high in retinol (preformed vitamin A), especially if they have other risk factors for osteopenia, and should avoid vitamin A supplements, including multivitamins containing preformed vitamin A, if their dietary intake is high.

Vitamin C

• found in citric fruits and many types of vegetables. • Vitamin C may have a minor role in preventing the

common cold, specifically for persons involved in high-intensity physical activity in extreme cold climates.

common cold,

• Large randomized trials have found no reduction in cancer in patients given vitamin C supplementation cancer

• Randomized trials have shown no benefit of vitamin C for primary or secondary prevention of coronary heart disease (CHD)

Cardiovascular disease

Kidney stones

Vitamin C increases urinary oxalate excretion and may increase the risk of kidney stones.

Vitamin E

SOURCES

alpha-tocopherol

•abundant in olive and sunflower oils, and is the predominant form in the European diet•The primary bioactive form of vitamin E•Alpha-tocopherol has eight isomers, but only four of these (RRR-, RSR-, RRS-, and RSS-are efficiently maintained in human plasma

Gamma-tocopherol

•is abundant in soybean and corn oil, and is common in the American diet.

RRR-isomer (formerly and incorrectly called D-alpha-tocopherol) is the only form found in foods; it is sometimes known as "natural source"

vitamin E.

Many synthetic vitamin E supplements or fortified foods contain all the eight isomers of alpha-tocopherol; these are known as "all racemic" or "DL" alpha tocopherol, and have

approximately half of the activity of "natural source" vitamin E

Synthetic vitamin E contains seven other isomers (termed "all-racemic vitamin E" or

DL-alpha-tocopherol), and has lower activity and possibly more toxic potential

than the RRR-isomer. ).

1 mg RRR-alpha tocopherol = 1.47 international units "natural source" vitamin E (D-alpha-tocopherol) = 2.2 international units "all

racemic" vitamin E (DL-alpha-tocopherol).

ACTIONS of Vitamin E as alpha-tocopherol)

works as a free radical scavenger,

vitamin E are independent of the antioxidant/radical scavenging activity, including inhibition of cell proliferation, platelet aggregation, and monocyte adhesion

Deficiency of vitamin E has been connected to cardiovascular events

, trials of vitamin E supplementation (which typically use "all-racemic" vitamin E) have generally shown no effect in prevention of

heart disease

Like other fat-soluble vitamins, bioavailability of alpha-tocopherol depends upon physiologic mechanisms for fat digestion and absorption.

This process requires lipolytic function of pancreatic enzymes

REQUIREMENTS

daily allowance (RDA) for vitamin E is 15 mg of dietary alpha-tocopherol per day for adolescents and adult men and women

This is the equivalent of 22 international units of RRR-alpha-tocopherol (the form that is supplied by some

supplements and is marketed as "natural-source" vitamin E), or 33 international units of all-rac-alpha-

tocopherol (the synthetic form used for the majority of supplements)

The recommended UL is 1000 mg of alpha-tocopherol daily (approximately 1,500 international units of natural source or 2,200 international units of synthetic vitamin E) for adults without fat malabsorption or other cause of vitamin E malabsorption.

We do not recommend supplementation near this level except when necessary to correct a deficiency state.

Most studies suggest that pharmacological doses of vitamin E supplementation in doses of 100 to 400 international units (67 to 272 mg RRR-alpha tocopherol) per day are safe for most patients

). Vitamin E supplementation with a dose ≥400 IU/day was associated

with a significantly increased risk of all-cause mortality

The benefit of vitamin E supplementation in pharmacologic doses on cancer, cardiovascular disease, stroke, dementia, and liver disease (such as nonalcoholic fatty liver disease) continue to be evaluated.

Effective serum vitamin E level = Alpha-tocopherol / (cholesterol + triglycerides)

A normal ratio is >0.8 mg alpha-tocopherol/gram total lipids.

Overview of dietary trace minerals

•minerals that are required by adults in amounts greater than 100 mg/day or make up less than 1 percent of total body weight

Macrominerals

•defined as minerals that are required in amounts between 1 to 100 mg/day by adults or make up less than 0.01 percent of total body weight

Trace elements (or trace minerals)

•are defined as minerals that are required in amounts less than 1 mg/day

Ultra-trace minerals

CHROMIUM

• — In 1957, a compound extracted from pork kidney was termed "glucose tolerance factor" because it corrected hyperglycemia in rats

• Glucose tolerance factor was ultimately found to be chromium (Cr).

. Cr supplementation in DM patients improved glucose tolerance and respiratory quotient, which indicates a

preference for fat metabolism and reduced utilization of carbohydrates as an energy source

•grains, cereals, fruits, vegetables, and processed meats•absorbed predominantly in the small intestine and is transported in the circulation bound to albumin and transferrin

Dietary source

s

•setting of zinc and iron deficiency, •suggesting that these minerals compete for intestinal absorption •Vit C

enhanced absorptio

n

•include certain drugs such as antacids, which contain magnesium, calcium, or aluminum salts. •Nonsteroidal antiinflammatory drugs that inhibit the production of prostaglandins also reduce Cr absorption

Decreased

absoption

Deficiency

TPN

hospitalized patients with increased catabolism and metabolic demands in the setting of malnutrition

short bowelsyndrome,

burns,

traumatic injuries

dietary reference intake

— The adequate intake of Cr for adults is 20 to 35 mcg per day

There is little evidence to support Cr

supplementation in individuals without Cr

deficiency.

COPPER

• The variability in the copper content of food reflects the variability in the copper content of soil.

• The acidic environment in the stomach facilitates solubilization of copper by dissociating it from copper containing dietary macromolecules

Risk factors for Copper deficiency

Foregut surgery, including gastrectomy or gastric bypass

Premature infants receiving milk formulas without adequate copper supplementation

Chronic diarrhea or other malabsorptive conditions including celiac disease

Chronic peritoneal dialysis or hemodialysis

Excessive zinc ingestion

The RDA for copper is 340 mcg daily for young children and rises to 900 mcg daily for adults [

The UL is 1 mg daily in young children and 10 mg daily for adults

IODINE

• dietary importance of iodine lies in the metabolism and homeostasis of the thyroid gland

• Iodine deficiency is associated with goiter, hypothyroidism, mental retardation, and increased neonatal and infant mortality.

The RDA for iodine is 90 mcg daily for children 1 to 8 years old, 120 mcg for children 9 to 13 years,

and rises to 150 mcg daily for older adolescents and adults.

During pregnancy and lactation, the RDA is 220 and 290 mcg daily, respectively

IRON

• Body contains3.5 gr iron ( 2.5 gr founfd in Hgb)• Mostly stored as ferritin or hemosiderin in liver , spleen ,BM,

hepatocyte• Despite RBC turnovering , Iron stores are well preserved as

iron is recovered• Only 0.5-1 mg / day is lost and more during mense &

pregnancy • 10% of Iron from diet is absorbed so we need 10 – 12 mg

iron /day• GI absorption is increased to 3- 5 fold during Iron deficiency • Animal sources( hem iron ) absorbed better than nonhem

Choice of preparation• Ferrous fumarate – 33 % Fe• Ferrous sulfate 20 %• ●Ferrous gluconate – 11%

There is no evidence that one of the above iron preparations is more effective than another for this purpose.

A large number of other oral iron-containing preparations and nutritional supplements are available, including the heme iron polypeptide Proferrin. They are generally more expensive than those described above and may not have been subjected to randomized clinical trials in patients with iron

deficiency. Some (eg, enteric coated, sustained release preparations) may be both

more expensive and poorly absorbed.

Accordingly, we do not recommend their use.

MANGANESE

• Meat, fish, poultry, dried fruit, and nuts are good sources of manganese, but absorption is very variable

Dietary sources —

•high dietary intakes of calcium, phosphate, and fiber

Absorption is decreased

•in the setting of iron deficiency

Absorption is icreased

Deficiency leads to poor growth, decreased fertility, ataxia, skeletal deformities, and abnormal fat and carbohydrate metabolism

• Manganese deficiency in humans is very unusual, but has been reported in individuals on a highly restricted diet.

— The recommended intake for manganese is expressed as an Adequate Intake (AI), because of the limited data available to

determine the population needs

The tolerable upper limit for manganese is 2 mg daily in toddlers, and up to 11 mg daily for adults

SELENIUM

•Seafood, kidney and liver, and meat are good sources of selenium source

•associated with skeletal muscle dysfunction and cardiomyopathy and may also cause mood disorders and impaired immune function , macrocytosis, and whitened nailbeds [

Deficiency

•(TPN) were historically not supplemented with selenium. Several cases of selenium deficiency in chronic TPN users have been reported with cardiomyopathy and skeletal muscle dysfunction

potential roles

• A number of studies have shown a linear relationship between selenium deficiency and a reduction in CD4 cell counts in HIV-infected patients

• Natural killer cell activity is enhanced when selenium is supplemented in the diet of selenium depleted individuals

Immune function

• studies support a possible relationship between Se and cancer mortality

• As a result, a number of studies have investigated the role of selenium supplementation for prevention of cancer

Cancer• In theory, the antioxidative effect protects lipid

membranes, inhibits oxidative modification of low density lipoprotein, and suppresses platelet aggregation

Cardiovascular disease

• — Animal models suggest that low doses of selenium may improve glucose metabolism,

• clinical studies in humans suggest that selenium supplementation does not confer benefit and may increase the risk of type 2 diabetes

Glucose metabolism

supplementation may be beneficial for individuals with low selenium intake, but could be detrimental to those with normal or high selenium intake

Selenium toxicity occurs with excess dietary intake, either through diets naturally high in selenium or "megadose" supplementation

The RDA for selenium is 20 mcg daily for young children,

rising to 55 mcg daily for adults

ZINC

• In 1961, a link was established between zinc deficiency, endemic hypogonadism, and dwarfism in rural Iran

• zinc deficiency may significantly increase the incidence of and morbidity and mortality from diarrhea and upper respiratory tract infections

• Meat and chicken, nuts and lentils are excellent sources

Along with iron, iodine, and vitamin A, zinc deficiency is one of the most important micronutrient deficiencies

globally

Deficiency

• Mild dietary zinc deficiency impairs growth velocity while severe depletion of zinc leads to growth retardation.

• Other clinical manifestations of zinc deficiency include delayed sexual maturation, impotence, hypogonadism, oligospermia, alopecia, dysgeusia (impaired taste), immune dysfunction, night blindness, impaired wound healing, and various skin lesions

• zinc deficiency, have been described in chronic diseases such as malnutrition, malabsorption syndromes (such as chronic inflammatory bowel disease), prolonged breastfeeding,pregnancy, elderly individuals with poor diet quality & gastric bypass for obesity and TPN

In these cases, the dietary zinc deficiency may have been exacerbated by medications that increase urinary losses of zinc,

including thiazides, loop diuretics, and angiotensin receptor blockers.

Zinc supplementation in diabetic patients may improve immune function, but also increases the HbA1c levels and leads to

worsening glucose intolerance

Zinc has also been used to treat the common cold, but probably has little

clinical value.

Zinc supplementation during pregnancy for women with mild zinc deficiency appears to promote fetal growth and reduce the risk of premature birth and

infant diarrhea

Mild zinc deficiency appears to be common, especially in developing countries. Individuals in developing countries are at risk of zinc deficiency because the diet is relatively low in zinc and contain significant amounts of phytates (which reduce zinc absorption

There is some evidence supporting the role of zinc supplementation to increase growth velocity in children, and several studies have suggested a benefit of zinc supplementation in children with acute diarrhea in developing countries

rising from 3 mg daily in early childhood to 8 mg daily for adult women, and 11 mg daily for adult men. Requirements are slightly higher during pregnancy and lactation

Nutrient-Nutrient Interaction In Multivitamin Supplements

do the nutrients in multivitamin/mineral supplements interact in any way that could damage (or maybe enhance) their

efficacy in the body?

• It sounds convenient to take one dose of a multivitamin a day and be done with it.

• However, doing so would actually work against your efforts to cover all your bases on vitamin and mineral needs. This is because several micronutrients impair the uptake of other micronutrients.

• You could say that they essentially cancel each other out. • But few supplement companies will actually educate you on this

fact. Instead, they prey on the consumer’s wish for convenience and create products based on convenience, not science.

• producing multivitamins that are devoid of critical micronutrients or in far too inadequate doses to be of any real benefit.

• Copper and zinc are chemically similar to iron. Since absorption is a process dictated entirely by chemistry (charge, molecular shape, etc.), copper, zinc, and iron all share similar absorption mechanisms.

• receptor has been shown to be involved in the absorption of not only iron, but also copper and zinc - although with different affinities for each mineral.

• Studies have shown that it has the highest affinity for iron. • So what does this mean on a nutritional level? If these nutrients

were to be taken at the same time, its likely that some nutrients will be left out unabsorbed and, effectively, useless to the body.

• The acidic environment in the stomach facilitates solubilization of copper by dissociating it from copper containing dietary macromolecules

• Deficiency neurologic manifestations include ataxia, neuropathy, and cognitive deficits that can mimic vitamin B12 deficiency

• Hematologic features of copper deficiency include anemia (usually microcytic) and neutropenia

• If iron supplements are given, these can worsen copper deficiency because excess iron competes with copper and decreases net copper absorption

Iron, Copper & Zinc

• It is suggested that supplemental iron (38-65 mg/day), but not dietary levels of iron, may decrease zinc absorption and substantially impact copper absorption.

• Similarly, competition studies have shown that high levels of zinc and copper may interfere with iron uptake.

• While some data suggests that zinc has no effect on copper absorption when given as a one-time mixture, clinical study has noted that taking large quantities of zinc (50 mg/day or more) for several weeks significantly impact copper bioavailability.

• It is thought that high zinc intake induces the production of a copper-binding protein, which “traps” the mineral and prevents its absorption

• Magnesium and manganese, two common minerals found in multivitamin supplements, also interact with iron.

• Magnesium may decrease non-heme iron absorption if the two nutrients are taken together.

• Calcium is suggested to decrease non-heme iron absorption when both are consumed at the same meal. This may only be a problem in those who are initially iron-deficient, suggests the National Institutes of Health (NIH).

• If you are iron-deficient or think you are at risk for deficiency, the NIH recommends to “minimize this interaction by separating your intake of calcium and iron.”

Iron, Calcium, Magnesium & Manganese

• Vitamin C, an antioxidant found in all of our tested multivitamins, is suggested to enhance non-heme iron absorption when both nutrients are eaten together, according to the CDC.

• Vitamin A – beta-carotene, specifically - also appears to enhance iron absorption, according to the National Institutes of Health. It is suggested to move iron from its storage site to red blood cells, where it is used to build hemoglobin. However, studies suggest that vitamin A is unlikely to enhance iron absorption in those who have adequate levels of vitamin A; it is more likely to improve iron status in those with low levels of vitamin A.

Iron & Vitamins C and A

• According to “An Evidence-Based Approach to Vitamins and Minerals,” vitamin A (in high doses) may reduce absorption of vitamin K.

• Nutrient interactions can vary in nature; that is, affecting absorption may not be the only way in which vitamins can influence the activity of other vitamins.

• As it turns out, vitamin E has a similar overall effect on vitamin K as does vitamin A, although not by inhibiting its absorption. Vitamin E achieves functional vitamin K deficiency by inhibiting the activity of vitamin-K dependent enzymes – effectively rendering vitamin K useless, even if it is absorbed

Vitamin A, E & K

• Zinc can inhibit amino acid uptake! • Since it’s important to take a multivitamin with a meal, such

as breakfast, a multivitamin that includes zinc could interfere with your body’s ability to take up the amino acids from the protein you consumed at breakfast. And that could interfere with muscle growth

• Zinc also interferes with copper uptake. Copper is something that you do want in your multivitamin.

• Zinc induces the intestinal synthesis of a copper-binding protein called metallothionein. Metallothionein traps copper within the cells in the intestines and prevents its absorption into the bloodstream

• iron interferes with zinc absorption,• you should skip the zinc until another time of day

Calcium is another big problem in multivitamin supplements

• Calcium interferes with zinc, iron and manganese absorption

• So these two minerals, calcium and magnesium, should also be completely absent from your multivitamin and be taken separately at another time of day.

Phosphorus is a fourth mineral that you do not

want in your multivitamin. The typical diet is already quite rich in phosphorus.

Having it in your multivitamin may raise

phosphorus levels too high

problematic because it can prevent the conversion of vitamin D to its active form, 1,25-dihydroxyvitamin D, in the kidneys.

Missing Multis

Another problem with most multis is that they completely skip out on some critical micronutrients altogether such as

vit K , iodine, chromium,copper

• . Recent research suggests that far more people are deficient in vitamin K than originally believed.

• Research also shows that supplementing with vitamin K2 alleviates the symptoms of vitamin K deficiency and provides a host of health benefits, including protection against heart disease and cancer, enhanced brain function, skin health, boosting testosterone production and promoting the formation of bone

vit K

• Another missing or under-dosed micronutrient in many multis is iodine, which is critical for maintaining healthy thyroid function

• So if your multi is not proving you iodine at 100% of the DV or RDA, then it’s a problem

iodine

• usually absent or severely under dosed.• This is problematic because most diets are quite

low in chromium• You could take a separate chromium

supplement, but this is one of the minerals that is best to get in your multivitamin.

• That’s because chromium uptake is enhanced when it’s taken at the same time as vitamin C, which should be in your multi.

chromium

• another mineral often missing completely or present in an adequate amount.

• Since higher intakes of zinc can lead to copper deficiency, and you should be certain to get 30 mg of zinc daily (separate from your multivitamin),

• Evidence suggests that you should get copper and zinc at a 1:10 ratio for optimal health.

• Since you should be getting in 30 mg of zinc each day, your multivitamin should provide a full 3 mg dose of copper

Copper

Vitamin and Mineral Dusting

• Vitamin K, iodine, chromium, copper, selenium and the B vitamins are all typically under dosed, if included at all, in most multivitamins.

• Other minerals that are also usually under dosed include selenium, molybdenum and manganese.

• These minerals and vitamins should at the very least provide 100% of the Daily Value (DV) or RDA for them.

Wrong Form

Most multis also use cheap, ineffective, or even potentially dangerous forms of certain vitamins and minerals

• Vitamin A is often provided in multivitamins mainly as preformed vitamin A (retinol) in the form of retinyl palmitate or retinyl acetate.

• These forms are rapidly absorbed, but slowly cleared from the body, which can lead to toxicity and liver problems if too much is consumed.

• Beta-carotene, on the other hand, is a much safer form of vitamin A to take as it only becomes active vitamin A when needed in the body.

• To avoid possible vitamin A toxicity, your multivitamin should provide all of its vitamin A from beta-carotene.

vitamin A

• K1: comes from plants, specifically green leafy vegetables, such as lettuce and spinach, as well as broccoli. Although this form of vitamin K is fine, it is not that necessary in a multivitamin since few people are vitamin K1 deficient.

• K2(menaquinone): comes from fermented products, such as cheese & fermented soybeans.

Vitamin K

. While both vitamins K1 and K2 appear to be involved in blood clotting, K2 provides benefits that go far beyond that.

Research suggests that being deficient in vitamin K may lower testosterone levels

The body requires so little vitamin K1 that just about everyone gets enough from their diet. Vitamin K2, on the other hand is required at a

much higher dose and provides more benefits

dietary requirement vit K , expressed as adequate intake (AI) is 90 micrograms daily in

women and 120 micrograms daily in men

• another mineral that is typically given in a cheap, less-effective form, such as chromium chloride

• Chromium picolinate is a combination of chromium and picolinic acid. The addition of the picolinic acid enhances the uptake of chromium.

Chromium

• Many companies will try to tell you that methylcobalamin is the best form of B12 to use. While this is one of the active forms of B12, it just one of the active forms.

• There are two active of forms. The other active form of B12 is adenosylcobalamin, also known as dibencozide.

• While some multivitamins provide both of these, the problem is the stability of these active forms.

• There is evidence that they are not very stable and therefore, do not provide the actual dose of B12 listed on the label.

• The only way to consume a stable form of B12 that is readily converted to both methylcobalamin and adenosylcobalamin in the body is by taking the cyanocobalamin form of B12.

vitamin B12

Coenzyme Q10

Coenzyme Q10 is involved in ATP generation

It functions as a lipid-soluble antioxidant

Its reduced form, CoQH2,inhibits protein and DNA oxidation

It has been suggested that CoQH2 is a more efficient antioxidant than vitamin E its tissue (but not blood)

concentration exceeds severalfold that of vitamin E

Coenzyme Q10

In human organs, the coenzyme Q content increases three- to fivefold during the first 20 years after birth,followed by a continuous decrease, so that in some tissues the concentration may be lower at 80 years than at birth

Coenzyme Q10 (CoQ10)

Acute myocardial infarction: 120 mg/day

AIDS: 200 mg/day

Alzheimer's disease: 120 mg 3 times/day

Angina: 60 mg/day

Breast cancer: 90 mg/day in combination with multivitamin/multimineral supplementation

Cardiomyopathy: 100-600 mg/day

Coenzyme Q10 (CoQ10)

Cardioprotection during surgery: 150 mg/day for 7 days prior to bypass surgery; 600 mg in divided doses in the 24 hours prior to surgery

Congestive heart failure: 2 mg/kg/day or 100-600 mg/day

Exercise performance: 90 mg/day

Hypertension: 75-360 mg/day; average dose: 225 mg/day

Migraine: 100 mg 3 times/day

Coenzyme Q10 (CoQ10)

Muscular dystrophy: 100 mg/day in divided doses

Parkinson's disease: 300-1200 mg/day

Periodontal disease: 5 mL/day of 200 mg/mL CoQ10 dispersed in corn oil divided doses

INTERACTIONS Depletion

CoQ10 may decrease response to warfarin

Hydralazine, thiazide diuretics, HMG-CoA reductase inhibitors, sulfonylureas, beta blockers, tricyclic antidepressants, chlorpromazine, clonidine, methyldopa, diazoxide, biguanides, haloperidol.

REPORTED INTERACTIONS

Coenzyme Q10

Various degrees of myopathy, myalgia, and rhabdomyolysis have been reported in statin-treated patients, and it is possible that these conditions are related to decreased muscle coenzyme

Q content.

Acetyl-L-carnitine/"-lipoic acid supplements

as a popular combination anti-aging

• A report that combined lipoic acid and dimercaptosuccinic acid provided therapeutic benefits to reduce renal damage from lead acetate in male Wistar rats (Sivaprasad et al., 2004).

• A report that "-lipoic acid treatment partially but significantly reversed diabetes in streptozotocin diabetic rats (Kumar & Prashanth, 2004).

• A report that lipoic acid pretreatment attenuated ferric chloride-induced seizures in male S-D rats (Meyerhoff et al., 2004).

• A report indicating that acetyl-L-carnitine had beneficial effects in animal models of Parkinson’s disease (Beal, 2004

• Supplemental "-lipoic acid is currently used in Germany to treat peripheral nerve degeneration resulting from diabetes.

• It has also been used as a therapeutic agent for hepatic coma, chronic hepatitis, cirrhosis of the liver, and has been partially successful in treating glaucoma

There are no standard doses for acetyl-L-carnitine and "-lipoic acid supplements. The highest doses

recommended for acetyl-L-carnitine (no salt specified) and for "-lipoic acid are 1,500 and 600

mg/day, respectively

QUERCETIN

• has antioxidant and anti-inflammatory effects which might help reduce prostate inflammation

• Quercetin is a plant pigment (flavonoid).• It is found in many plants and foods, such as red

wine, onions, green tea, apples, berries, Ginkgo biloba, St. John's wort, American elder, and others. Buckwheat tea has a large amount of quercetin.

• People use quercetin as a medicine.

Quercetin is used for treating conditions of the heart and blood vessels including

• (atherosclerosis), high cholesterol, heart disease, and circulation problems. It is also used for diabetes, cataracts, hay fever, peptic ulcer, schizophrenia, inflammation, asthma, gout, viral infections, chronic fatigue syndrome (CFS), preventing cancer, and for treating chronic infections of the prostate. Quercetin is also used to increase endurance and improve athletic performance.

CHOLINE

How does it work?

• Choline is similar to a B vitamin.• It is also found in foods such as liver, muscle meats, fish,

nuts, beans, peas, spinach, wheat germ, and eggs.

• It is used in many chemical reactions in the body.

• Choline seems to be an important in the nervous system.

• In asthma, choline might help decrease swelling and inflammation

Potential role • Choline is used for liver disease, including chronic hepatitis and cirrhosis.

It is also used for depression, memory loss, Alzheimer's disease and dementia, Huntington's chorea, Tourette's disease, a brain disorder called cerebellar ataxia, certain types of seizures, and a mental condition called schizophrenia.

• Athletes use it for bodybuilding and delaying fatigue in endurance sports.

• Choline is taken by pregnant women to prevent neural tube defects in their babies and it is used as a supplement in infant formulas.

• Other uses include preventing cancer, lowering cholesterol, and controlling asthma.

COLLOIDAL MINERALS

• Colloidal minerals are taken from clay or shale deposits..

• Despite safety concerns, colloidal minerals are used as a supplemental source of trace minerals and as a dietary supplement to increase energy.

• They are also used for improving blood sugar levels in diabetes, treating arthritis symptoms, reducing blood cell clumping, reversing early cataracts, turning gray hair dark again, flushing poisonous heavy metals from the body, improving general well-being, and reducing aches and pains.

Inositol

• Inositol is a vitamin-like substance. It is found in many plants and animals. It can also be made in a laboratory.

• Inositol is used for diabetic nerve pain, panic disorder, high cholesterol, insomnia, cancer, depression, schizophrenia, Alzheimer’s disease, attention deficit-hyperactivity disorder (ADHD), autism, promoting hair growth, a skin disorder called psoriasis, and treating side effects of medical treatment with lithium.

• Inositol is also used by mouth for treating conditions associated with polycystic ovary syndrome, including failure to ovulate; high blood pressure; high triglycerides; and high levels of testosterone.

Lutein

• Lutein is called a carotenoid vitamin. It is related to beta-carotene and vitamin A. Foods rich in lutein include broccoli, spinach, kale, corn, orange pepper, kiwi fruit, grapes, orange juice, zucchini, and squash. Lutein is absorbed best when it is taken with a high-fat meal.

• Many people think of lutein as “the eye vitamin.” They use it to prevent eye diseases including age-related macular degeneration (AMD), cataracts, and retinitis pigmentosa.

• Some people also use it for preventing colon cancer, breast cancer, type 2 diabetes, and heart disease.

• Many multivitamins contain lutein. They usually provide a relatively small amount of 0.25 mg per tablet.

PARA-AMINOBENZOIC ACID PABA Overview Information

• Para-aminobenzoic acid (PABA) is a chemical found in the folic acid vitamin and also in several foods including grains, eggs, milk, and meat.

• PABA is taken by mouth for skin conditions including vitiligo, pemphigus, dermatomyositis, morphea, lymphoblastoma cutis, Peyronie's disease, and scleroderma. PABA is also used to treat infertility in women, arthritis, "tired blood" (anemia), rheumatic fever, constipation, systemic lupus erythematosus (SLE), and headaches. It is also used to darken gray hair, prevent hair loss, make skin look younger, and prevent sunburn.

• PABA is best known as a sunscreen that is applied to the skin (used topically).

• PABA doesn't seem to be taken by mouth as often as it used to be, possibly because some people question its safety and effectiveness

SAW PALMETTO

• Saw palmetto is a plant. Its ripe fruit is used to make medicine.

• Saw palmetto is best known for its use in decreasing symptoms of an enlarged prostate (benign prostatic hypertrophy, BPH). According to many research studies, it is effective for this use.

• Saw palmetto is used for treating certain types of prostate infections. It is also sometimes used, in combination with other herbs, to treat prostate cancer.

• Some people use saw palmetto for colds and coughs, sore throat, asthma, chronic bronchitis, chronic pelvic pain syndrome, and migraineheadache. It is also used to increase urine flow (as a diuretic), to promote relaxation (as a sedative), and to enhance sexual drive (as an aphrodisiac).

RICE BRAN

• Rice bran is used for treating diabetes, high blood pressure, high cholesterol, alcoholism, obesity, and AIDS;

• for preventing stomach and colon cancer; • for preventing heart and blood vessel (cardiovascular) disease;• for strengthening the immune system; • for increasing energy and improving athletic performance; • for improving liver function; and • as an antioxidant.

• Rice bran oil is also used for high cholesterol.

• Some people apply rice bran directly to the skin for an allergic skin rash called eczema (ectopic dermatitis).

• Any question ?