The case against nutritional supplements

Todd Becker gettingstronger.org

Ancestral Health Symposium

August 17, 2013

How did our ancestors thrive without supplements? Do we really need them?

Main Thesis

• For most* people, routine supplementation with vitamins, minerals and essential fatty acids is unnecessary and may be counterproductive

• A paleo diet and lifestyle – enhanced by hormesis – reduces or eliminates the need for supplementation

* Caveat: Short term supplementation may be advisable in cases of malnutrition, infection, illness, pregnancy or special athletic goals.

Outline

• The case for nutritional supplements

• General doubts and objections

• Four examples

– Antioxidants

– Vitamin D

– Calcium

– Omega-3 fatty acids

• The role of hormesis

The “paleo” case for nutritional supplements

• Inability to synthesize (vitamin C)

• Inefficient synthesis (vitamin D, omega-3)

• Deficient soils and oceans (minerals, omega-3)

General doubts and objections

1. You are not what you eat

You are what your body does with what you eat

This applies to macronutrients

• Excess glucose triglycerides

• Excess protein glucose

• Soluble fiber short chain fatty acids

General doubts and objections

1. You are not what you eat

You are what your body does with what you eat

But it also applies to micronutrients

• Malabsorption / excretion (calcium)

• Oxidation (antioxidants, fatty acids)

• Hormone signaling (vitamin D)

• Gene expression (antioxidants, vitamin D)

General doubts and objections

2. Nutrients are regulated homeostatically

Exogenous nutrients

can downregulate endogenous defenses

Examples

– Antioxidants – Vitamin D

The case for antioxidants

• Reactive oxygen species (ROS)

• Can’t synthesize our own vitamin C

• Mega doses suggested for: – Common cold – Infections – Cancer

• Other antioxidants • Vitamin A • Vitamin E • Beta carotene • Co-Q10 • Alpha lipoic acid

Fruits & vegetables

• Health benefits of fruits and vegetables “ associated” with antioxidant content

?

Interventional studies show no benefit …or even positive harm

AMA (2004):

Meta-analysis 20 studies: C, E beta carotene > No reduction in CVD, stroke or mortality

Cochrane (2008):

Meta-analysis 67 studies: A, C, E, selenium > No reduction in mortality Antioxidants adversely impact exercise!

Ristow (2009): Vitamins C and E + exercise for 4 weeks > decreased insulin sensitivity improvement > reduced antioxidant enzyme levels

Before exercise

After exercise

What could be going wrong?

• Oxidative “stress” by ROS is not always bad!

• ROS are essential for cell signaling, exercise regulation, and fighting infection

• Moderate ROS plays a hormetic role in improving mitochondrial function and upregulating endogenous antioxidant enzymes

• Antioxidant supplements indiscriminately suppress cell signaling and downregulate endogenous antioxidant enzymes

Endogenous Antioxidants

• The xenobiotic metabolism produces Phase II antioxidant enzymes to catalytically neutralize chemical toxins: – Superoxide dismutase (SOD), glutathione reductase (GSH), etc.

• We have co-evolved with certain edible plants to tolerate modest amounts their polyphenolic “toxins”

• Exposure to these polyphenolic “hormetins” activate the Nrf2 pathway, which produces the endogenous antioxidants

• Hormetins are abundant in pigmented, bitter plants and herbs

• Resveratrol

• Sulforaphane

• Curcumin

• Green tea

Supplements vs. Hormetins

Supplements: Antioxidants, minerals, vitamins and essential fatty acids taken to correct apparent deficiencies

Hormetins: Spices, herbs, phytonutrients that activate and strengthen the body’s endogenous processes of defense, repair, and tolerance and performance.

Typically hormetins work synergistically and at low dose

Hormetins are agents of hormesis

• Dose-response effect

• Stressors we’ve evolved with

• Activate Defense & repair mechanisms

Edward Calabrese

Suresh Rattan

Many examples of hormesis

• Chemicals

• Sunlight (UV)

• Ionizing radiation

• Exercise

• Barefoot running

• Fasting / Ketosis

• Cold exposure

• Immunotherapy

• Vision Improvement

Vitamin C recycling

• Vitamin C (ascorbate) neutralizes oxidants 1-for 1

• Dehydroascorbate (oxidized vitamin C) is readily recycled thousands of times by endogenous glutathione reductase

• Elevated blood glucose inhibits reuptake and recycling of dehydroascorbate

ROS

Vitamin C storage

• Advocates of mega dose vitamin C note that most primates (simians) consume 10-20X the RDA of vitamin C

• But humans can efficiently store 10-100X the blood levels of vitamin C in adrenal, thymus, pituitary and other glands – enough to ward of scurvy for 3-8 months

Antioxidants: Take home message

• Based upon adequate storage and catalytic recycling, a low glycemic diet rich in hormetic polyphenols greatly decreases the daily need for dietary and supplemental vitamin C

The case for vitamin D

• From diet or action of UV on skin

• D3 itself is not biologically active

– Requires liver & kidney conversions

– Active form (1,25-D) binds VDR receptor

• Vitamin D has a dual function

– Low dose: calcium absorption

– Higher dose: immune function (VDR)

Correlation and causation

• Low vitamin D3 levels correlate with higher heart disease, stroke, immune problems, infection & overall mortality

• But is low vitamin D3 a cause – or a consequence – of ill health?

– Healthy people may get more sun and exercise, elevating D3

– People with low D3 often have elevated 1,25-D

• Could 25-D be a mere “biomarker” for health status?

Vitamin D risks & questions

• Interventional studies show no benefit, possible harm:

– AMA(2010): Supplements for 5 years in women over 70 produced 15% more falls and 26% more fractures

– NCI (2012): Elevated 25-D linked to aggressive prostate cancer

• Vitamin D is a secosteroid – binds the VDR receptor

– VDR activation dampens the innate immune response

– Provides short term control of infection and autoimmunity

– Long term supplementation with the inactive 25-D might inhibit 1,25-D action and/or down-regulate VDR function

An alternative to vitamin D?

• Can we get the benefits of Vitamin D without the risks of daily supplementation or sun exposure?

• Hoyer-Hansen studied the pathways activated by the VDR receptor and noted that

“Autophagy could be a general mediator of the health-promoting effects of 1,25-(OH)2 (D3). Accordingly, there is a striking overlap among the diseases promoted by VD deficiency and defective autophagy.”

Autophagy

• A cellular housecleaning process – Recycles damaged cytoplasmic matter – Activated by calorie restriction and exercise

• Regulates the same pathways as vitamin D receptor – Inhibits mTOR, bcl-1, bcl-2 – Inhibition of carcinogenesis and tuberculosis

Take home message – Vitamin D • Be wary of supplementing , especially at high doses • Consider that intermittent fasting and exercise might

activate the same metabolic benefits

The case for calcium supplements

• Strong bone formation requires an adequate supply of calcium

• Deficiencies of calcium (and vitamin D) lead to rickets and osteoporosis

What do interventional studies show?

• Harvard study of 77,761 nurses for 12 years showed no protection from bone fractures at any dose of calcium (from dairy or supplements)

• Confirmed by similar studies in Australia and the UK

Is calcium getting to where it is needed?

• Blood levels of calcium are tightly regulated

• High levels of vitamin D deplete vitamin K2 and promote calcification of vascular tissue

• On a standard diet high in grains, phytates bind calcium, leading to poor absorption

• High blood glucose and insulin levels “leach” calcium from bones

• In short, taking calcium supplements doesn’t ensure it will get into bones

A better way to build bones

• The solution is not supplementation, but a whole food diet of “available” calcium, with vits. D, A, K2

• Weight bearing exercise is the most practical way to stimulate uptake of calcium into bones

The case for omega-3 supplements

• EPA and DHA are long chain essential N-3 fatty acids (EFAs), critical to brain, eye and heart function

• A low n-3/n-6 ratio has been linked to CVD, Alzheimer’s, depression, autoimmune disorders

• Most Westerner’s show poor enzymatic conversion of shorter chain n-3s to the EFAs

• EFAs from consumption of fatty fish is inadequate

Hence, dietary supplementation is recommended

Stillwell, William. “The role of polyunsaturated lipids in membrane raft function”, Scandinavian Journal of Food and Nutrition, 2006; 50 (S2): 107 -113.

However EFA supplements have a downside

• A 2013 JAMA study of 2000 men found that men with the highest blood levels of EPA and DHA had

– 71% higher risk of aggressive prostate cancer

– 44% higher risk of low-grade prostate cancer

• These results replicate earlier findings from a 2011 study

• Under-reported: The increased risk appears associated only with the more easily oxidized DHA, not EPA (Nina Bailey)

Diet impact on DHA “survival”

• Low carbohydrate diets dramatically increase “end product” DHA in muscle membranes – This improves insulin sensitivity and

inhibits lipogenesis

• This happens despite reduced enzymatic synthesis of DHA under carbohydrate restriction

• Low carb diets appear to help “preserve” DHA by suppressing ROS-driven lipid peroxidation

From Volek and Phinney, “The Art and Science of Low Carbohydrate Living” (2011)

Diet controls fate of EFAs

• DHA is less stable than EPA to lipid peroxidation. The higher association of DHA with cancer may reflect this fact.

• Low carb/paleo/non-inflammatory diets result in a reduced dietary requirement for EFAs because they are better “preserved” against oxidative damage and inter-conversion is optimized

• Thus, a non-inflammatory diet may be critical to getting EFA benefits without the risks posed by unstable and “damaged” DHA

Parting thoughts

• Recommended Daily Allowances for supplements came from studies of people eating Western diets

• Those diets oxidize nutrients, impair absorption and recycling, and downregulate endogenous defenses

• A low insulinogenic, non-inflammatory, whole food diet greatly improves micronutrient utilization

• Phytonutrients and hormesis can boost endogenous antioxidants and other defenses

For further reading

Related articles on my blog

gettingstronger.org

“The case against antioxidants”

“Why I don’t take vitamin D supplements”

“An alternative to vitamin D supplements”

References Antioxidants

1. Kris-Etherton, Penny M. et al, “Antioxidant vitamin supplements and cardiovascular disease” Circulation 2004, 110: 637-641.

2. Bjelakovic, Goran et al, “Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases”. Cochrane Database of Systematic Reviews 3: John Wiley & Sons, 2008 and updated 2012.

3. Cheung, M.C. et al, “Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL” Arterioscler Thromb Vasc Biol, 2001, Aug; 21 (8) 1320-6,

4. Ristow, Michael et al., “Antioxidants prevent health-promoting effects of physical exercise in humans” PNAS 2009 ; published ahead of print May 11, 2009, doi:10.1073/pnas.0903485106

5. Mendriatta, S. et al. “Erythrocyte ascorbate recycling: antioxidant effects in blood”, Free Radic Biol Med. 1998, 24 (5): 789-97.

6. Wang, Yaohui et al. “Ascorbate recycling in human neutrophils: Induction by bacteria” Proc. Nat Acad Sci of U.S.A., 1997, 94 (25) 13816-9.

7. Li, Guolin, “The Positive and Negative Aspects of Reactive Oxygen Species in Sports Performance”, Ch. 6 in Michael Hamlin et al., ed, Current Issues in Sports and Exercise Medicine, ISBN 978-953-51, 2013, -1031-6,, 2013

References 8. Rountree, Robert, “Beyond Antioxidants: Nutrigenomic Regulation of the Adaptive Stress

Response.” Integrative Practitioner, 2010. http://www.integrativepractitioner.com/article.aspx?id=17183

Vitamin D

9. Sanders, K.M. et al., “Annual High-Dose Oral Vitamin D and Falls and Fractures in Older Women: A Randomized Controlled Trial. JAMA 2010, 303 (18) , 1815-1822.

10. Masterjohn, C. “Vitamin D toxicity redefined: vitamin K and the molecular mechanisms” Med Hypotheses 2007, 8 (5): 1026-34.

11. Agus, David B., The End of Illness. New York: Simon & Schuster, 2011.

12. Hoyer-Hansen, M.D. “Autophagy as a basis for the health-promoting effects of vitamin D”. Trends in Molecular Medicine (2010) 16:7, 295-302

Calcium

13. Feskanich, D. et al. “Milk, dietary calcium and bone fractures in women: a 12-year prospective study” Am J Public Health, 1997, 87 (6) 992-7.

References Omega-3 fatty acids

14. Stillwell, William. “The role of polyunsaturated lipids in membrane raft function”, Scandinavian Journal of Food and Nutrition, 2006; 50 (S2): 107 -113.

15. Brasky, T. M. et al. “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial” Journal of the National Cancer Institute, Aug 7; 105 (15) 1132-1141, 2013

16. Bailey, Nina. “DHA, not EPA, responsible for omega-3 prostate cancer risk. Igennus Healthcare Nutrition blog, http://www.igennus-hn.com/dha-not-epa-responsible-for-omega-3-prostate-cancer-risk-by-dr-nina-bailey/

17. Volek, Jeff S. and Stephen D. Phinney. The Art and Science of Low Carbohydrate Performance: A Revolutionary Program to Extend your Physical and Mental Performance Envelope. Createspace.com, Chapter 9 and references, 2012

Hormesis

18. Calabrese, Edward J., and Linda A. Baldwin. "Hormesis: The Dose-Response Revolution." Annu. Rev. Pharmacol. Toxicol. 43: 175-97, 2003.

19. Rattan, Suresh I and Dino Demirovic. “Hormesis Can and Does Work in Humans.” Dose-Response. 8(1): 58-63, 2010.