NFS302 Week 8: Steroids and Supplements

Steroids

• Anabolic-Androgenic steroids (AAS) → named for the effect they elicit

• May have some legitimate clinical utility

  • Treatment for reproductive dysfunction, breast cancer, anemia, muscle loss (cachexia)

• Most famously used as illegal PEDs

  • All of these are made of synthetic versions of the hormone testosterone

Timeline of Steroid History

• 1849: transplant of chicken testicles into abdomen of castrated birds → androgenizing effects

• 1939: Butenandt wins Nobel Prize for work on sex hormones

• 1950s: Soviet Union begins giving steroids to weightlifters

• 1965: debut of Mr. Olympia show

• 1968: 1st Olympics with IOC banning PED use

• 1977: ACSM release paper claiming steroids are ineffective for muscle gains → hoped to discourage people taking them

• 1987: ACSM release update retracting previous statement

How do Steroids work?

Potential mechanisms:

• ↑ increase rate of muscle protein synthesis

• ↓ rate of muscle protein breakdown

• Inhibition of cortisol (“train harder”)

↑ rates of transcription of new proteins

Prevalence of Use Globally

• 187 studies including surveys from all 6 continents

  • Prevalence for males: 6.4%

  • Prevalence for females: 1.6%

• Use most prevalent among recreational sportspeople and athletes

• Use more prevalent among teenagers than 19+

Prevalence of use in Canada

• Aimed to examine and describe characteristics of AAS users among a national sample of Canadian adolescents/young adults aged 16-30 years

• Data from 2774 subjects from Canadian Study of Adolescent Health Behaviours were analyzed

• 1.6% (N = 44) report lifetime AAS use and 0.8% (N = 23) reported using AAS in the past 12 months

• AAS users by gender:

  • Men 81.8%

  • Women 13.6%

  • TGNC individuals 4.6%

Steroid Dosages

• Gains in strength and size only occur with doses of >300mg/week

• Nearly 70% of respondents in this sample took 500-1500mg/week

  • Way more than necessary

• TRT = 100-200mg/week

• Pro bodybuilders: 1000+ mg/week

• High-level bodybuilders: 5000+ mg/week

• “A lot” of steroids → >3000mg/week on average for the year, including orals and injectables

Effects of Steroids

• 40 men completed the study, randomized into 1 of 4 groups:

1. Placebo and no exercise

2. Placebo and exercise (weight training 3x/week)

3. Testosterone and no exercise

4. Testosterone and exercise (weight training 3x/week)

• Duration = monitored for 30 total weeks; 10 weeks of treatment

• Dose = 600mg/week injected intramuscularly

• To overcome the pitfalls of previous studies, intake of energy, protein and exercise stimulus were standardized

• Results =

  • Similar results for changes in strength

  • The % BF didn’t change significantly in any group

  • BUT big muscle tissue increase in group 3

Lance Armstrong

• Took steroids, banned from Tour de France

• No effect on endurance

• Steroids inhibit cortisol → better training

  • Allows them to train better

  • Took steroids and EPO

Negative Effects of Steroids

APEDs Research Report

• Steroid use can lead to early heart attacks, strokes, liver tumours, kidney failure and psychiatric problems

• Stopping may cause withdrawal

Negative Side Effects: Reproductive System

• This review included 33 studies for a total pool of 3879 participants

  • 1766 AAS users and 2113 non-AAS users

• The majority of the participants were men; only 6 provided data for female athletes

• Conclusion:

  • Majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and test levels

  • AAS use results in profound and prolonged effects on reproductive system and possibly effects on fertility

Negative Side Effects: Cardiomyopathy

• 101 weightlifting AAS users with at least 1-year cumulative AAS use vs. 71 non-using weightlifters

• AAS users had:

  • Higher left ventricular mass index

  • Worse left ventricular ejection fraction

  • Worse right ventricular global longitudinal strain

  • Higher systolic BP

Negative Side Effects: Brains

• Male weightlifters with a history of prolonged AAS use (n = 130) vs. a group with no AAS use (n = 99)

• Used MRI brain scans, compared gap between chronological age and Predicted Brain Age

• Conclusion:

  • AAS users had higher Brain Age Gap compared with weightlifting control subjects, which was associated with dependency and longer history of use

  • Group differences not explained by other substance use, general cognitive abilities, or depression

Negative Side Effects: Mortality

• Study of deaths in Denmark

• Identified males who received a doping sanction between 2006-2018

• For each AAS user, 50 male control participants from general population were randomly included through the Danish Civil Registration System

• Conclusion: hazard ratios were higher for both natural and unnatural deaths among AAS users vs. controls

Might Expect Different Side Effects on Females

• East Germany had an official policy of doping launched in the 1960s

• Court case following the fall of East Germany had 142 former female athletes as plaintiffs with all manners of horrendous outcomes

Association of Testosterone and CVD risk

• First 2 key points pertaining to TRT in older men:

1. Strong support of association of low testosterone concentration/hypogonadism with CVD events

   1. But low test may just be a marker, not a cause

2. TRT favourable changes many cardiovascular risk factors

• No compelling evidence that testosterone therapy either increases/decreases cardiovascular risk

5 Points to Summarize Steroid Side-Effects

1. There are likely different side effects on males vs. females

2. Most information comes from case reports rather than RCTs → difficult to get ethics approval administrating steroids

3. Any scientific work done is likely underestimating

   1. Subjects: difficult to get people who admit to taking illegal substances

   2. Doses: may be significantly less than what is taken in the real world

4. Any utility for older men (TRT) shouldn’t be extrapolated to young men taking steroids just to improve physique/athletic performance

5. “Only the dose makes the poison” - Paracelsus

Canadian Centre for Ethics in Sport (CCES)

• National not-for-profit organization

• 80% funded by the government (Sport Canada), 20% funded through their own revenue generating programs

• Mission → making sports better

• Oversees and administers the Canadian Anti-Doping Program (CADP) in compliance with international standards

World Anti-Doping Agency (WADA)

• Established in 1999 as an international independent agency composed and funded equally by the sports movement and governments of the world

• Sets the rules and regulations, standardizes anti-doping in sports

How much doping goes on? (2019)

• Canada: ~0.4% of population

  • 3161 tested, 13 found

• Globally: ~0.97% of population

  • 263,519 tested, 2774 found

What are athletes taking to cheat?

• Of the 12 Olympic games between 1968-2012, 134 medals were impacted by anti-doping rule violations (average of 11.1 medals/Olympic games)

  • 89% were from 4 Games since Sydney 2000

• 3 Olympics (2004, 2008, 2012): 142 athletes were identified to have committed anti-doping rule violations

• Exogenous AAS metabolites were present in 90% of all athlete samples

  • Athletics and weightlifting were the most affected sports (combined ~89% of the violations)

Doping Violations & Supplements: 2005-2013

• Australia: 172 doping violations, 11 associated with supplements, 6.4%

• UK: 68 doping violations, 6 associated with supplements, 8.8%

• US: 222 doping violations, 17 associated with supplements, 7.7%

The Prohibited List

• Official document published annually by WADA

• Identifies types of substances prohibited in sport, including:

  • Prescription medication

  • Non-prescription medication

  • Recreational drugs and substances of abuse

  • Prohibited methods of treatment

Global DRO

• Tool that allows you to search medications by brand, ingredient or drug identification number to check its status in sport

• Prohibited substances are identified as:

1. Prohibited in competition only

2. Prohibited at all times

3. Conditional/threshold

4. Prohibited by certain routes of administration

5. Prohibited by certain sports

Criteria for substances being prohibited

• A substance must meet 2 out of the 3 following criteria:

  1. Enhances performance

  2. Poses a health risk to the athlete

  3. Violates the spirit of the sport

Interesting Case Studies: Should vs. Shouldn’t be prohibited

• Cannabis:

  • Canadian snowboarder Ross Rebagliati won a gold medal at the 1998 Olympics but was stripped of it for testing positive for cannabis

  • Cannabis is not a performance enhancer

• High-tech suits in swimming:

  • Recently banned

Situations where dietary supplements could be effective

• Promoting overall health and wellbeing

• Women of childbearing age = folic acid to reduce the risk of neural tube defects

• Adults > 50 years old = Health Canada reocmmends a Vitamin D supplement of 400 IUs/day

• Strict vegetarians/vegans = vitamin B12, iron, zinc, EPA & DHA, methionine, leucine, choline

• Improving nutrient intake particularly of lower socioeconomic status groups

• Promoting “self-care” — leards to reduced burden/cost on healthcare system

• Optimizing athletic performance

IOC Consensus Statement

• Released a statement on dietary supplements and the high performance athlete

Andrew Huberman

• “A lot of these things we call supplements are very potent compounds that can transform our ability to perform in the short term, to recover from exercise, and that can really shape brain chemistry, hormone patterns…acutely and when taken long term”

Australian Institute of Sport (AIS)

• AIS sport supplement program is designed to provide world’s best practice in the research, education and provision of sports foods and supplements

AIS Group A

• Supported for use in specific situations in sport

  • Sports drink, gel, bar

  • Whey protein

  • Calcium, iron, zinc, vitamin D supplements

  • Multivitamin/mineral

  • Probiotics

  • Electrolyte replacement

  • Caffeine

  • Creatine

  • Bicarbonate

  • Beta-alanine

  • Beetroot juice

  • Glycerol

AIS Group B

• Emerging scientific support/deserving of further research

  • Fruit derived polyphenols

  • Vitamin C

  • Collagen

  • Carnitine

  • Ketone supplements

  • Fish oils

  • Curcumin

  • N-acetylcysteine

AIS Group C

• Scientific evidence NOT supportive of benefit amongst athletes, or no research undertaken to guide an informed opinion

  • Magnesium

  • Alphalipoic acid

  • HMB

  • BCAAs/leucine

  • Phosphate

  • Prebiotics

  • Vitamin E

AIS Group D

• Banned or at high risk of contamination with illegal substances - can lead to a positive doping test

  • Stimulants (ephedrine)

  • Prohormones and hormone boosters

    • Androstenedione

    • Tribulus terrestris

  • GH releasers

  • Beta-2 antagonists

  • Selective androgen receptor modulators (SARMs)

Placebo effect

• Physical or emotional change occurring after a substance is taken or administered that is not the result of any specific property of that substance

• The change may be beneficial, reflecting the expectations of the patient

2 Reviews of placebo effect

• No significant effects on objective outcomes; possible small benefits in studies with continuous subjective outcomes, i.e. pain, nausea

  • NEJM

  • Cochrane Database

• Study design testing placebo effect:

  • Crossover design, testing power production on 90 minute cycle ride, follosing supplement ingestion after overnight fast

  • Trial 1: just water = control (all 3 trials)

  • Trail 2: the nutritional supplement (water vs. 2 supps)

Regulatory Background of Food Supplements

• Key piece of legislation in Canada is the Food and Drug Act

  • Food and drug regulations

  • Natural health products (NHPs) regulations

• What is an NHP?

  • Vitamins and minerals

  • Herbal remedies

  • Homeopathic medicines

  • Traditional medicines such as traditional Chinese medicines

  • Probiotics

  • Other products: amino acids, essential fatty acids

• To be legally sold in Canada, a product must have:

  • Natural product number (NPN) - 8 digits

  • Drug identification number - homeopathic medicine (DIN-HM)

Why Do People try these things?

• People who had no further treatment options available to them

• Right to “try before you die”

Commentaries on the State of Regulations

• “The consequences of ineffective regulation of dietary supplements”

• “No regulatory double standard for natural health products” → Canadian medical association journal

  • Followup letter from Consumer Health Products Canada

Why do we have a problem?

Lun, Erdmann et al.

• Dietary supplementation practices in Canadian high performance athletes

• Asked what their primary source of supplement advice was?

  • Family, friends, coaches, teammates at the top

  • Registered dietitians ranked #16 on the list → very low

Dietetics Act, 1991 Ontario Regulation

• The following are acts of professional misconduct:

  • Item 14: Recommending vitamins, minerals or nutritional supplements for improper use

You can’t really be sure what you’re getting

• Depends if you have the supplement

• All happens in a dark cloud

• Depends if you have what you want to have

• Never really sure what you’ll get

How can a person be extra sure?

• NSF: an independent, not for profit organization, that helps protect you by certifying products and writing standards for food, water, and consumer goods

• LGC - Informed-Choice is a quality assurance program for sports nutrition products, suppliers to the sports nutrition industry, and supplement manufacturing facilities

  • Program certifies that all nutritional supplements and/or ingredients that bear the Informed-Choice logo have been tested for banned substances by the world class sports anti-doping lab LGC

Where are the Negative Consequences?

Lun, Erdmann et al.

• Dietary supplementation practices in Canadian high performance athletes

• Past studies have reported numbers as high as 99% of athletes take supplements

• this study of 440 high-level Canadian athletes found that 87% took a supplement within the last 6 months

• These authors wrote: “Most of the supplements reported in this research are unlikely to pose health risks”

70% of Canadians use NHPs on a regular basis - NHP industry is hige

Reports in Scientific Journals

• ATBC Cance Prevention NEJM:

  • Beta-carotene lead to 18% higher chance of lung cancer and 8% all-cause mortality in smokers

• Bjelakovic et al. 2008 Cochrane Database:

  • 20 randomized trials, 200k+ participants

  • “Antioxidants”: vitamins A, C, E, beta-carotene and selenium

    • Increase overlal mortality

• Lippman et al. 2009 JAMA:

  • “SELECT” trial of 35k+ men

  • Halted after 5 years due to implications that vitamin E and selenium were leading to increased incidence of prostate cancer

• Newmaster SG et al. 2013 BMC med:

  • Blindly tested the authenticity of 44 herbal products representing 12 companies using DNA barcoding

  • Samples collected from GTA

  • Able to authenticate 48% of the products tested; of these, 33% also contained contaminants and/or fillers not listed on the label

  • 59% of products tested contained species of plants not listed on the labels

• Geller IA et al. NEJM:

  • Data collected from 63 ERs across the USA between 2004-2013

  • Estimate that 23k+ ER visits/year in the US are attributed to adverse events from taking dietary supplements

• Gillard V et al. 2015:

  • Analyzed 150 supplements marketed to increase sexual performance

  • 61% contained some adulterant including 5.5% which contained drugs to treat sexual dysfunction

  • Only 31% of samples could be considered true herbal/natural products

• H Geyer et al. 2004 Int J Sports Med:

  • Collected 634 supplements from 215 suppliers in 13 countries

  • 94 supplements (~15%) contained anabolic androgenic steroids (unlabelled)

  • Authors speculated likely due to cross-contamination, but still could lead to doping violations