By Seán Finan
The FDA’s policy guidelines on nutritional fortification include the so-called “jelly-bean rule:” the FDA considers it inappropriate to fortify candy or soda with nutrients because to do so would allow “misleading health claims” to be made about a putatively unhealthy product. Candy companies that tried to add vitamins their products to market them as “healthier” have already been targeted by the FDA. But take a quick glance at the shelves of any convenience store: the “healthy”, vitamin enriched snacks and drinks are so full of sugars, flavors and sweeteners that it would take a doctorate in metaphysics, rather than medicine, to distinguish them from the candy and soda. So, maybe the FDA’s stance on adding a spoonful of sugar to help the medicine go down has relaxed. With that in mind, here’s a little thought experiment. I’d like to bring a proposal back from the eighties: that inexpensive alcoholic beverages be fortified with allithiamine, a fat-soluble analogue of Vitamin B1.[1] Why? The fortification could dramatically reduce the incidence of Wernicke’s encephalopathy and Korsakoff’s Syndrome among the homeless and alcoholic population.
What is Wernicke’s Encephalopathy?
First things first; a chronic deficiency in thiamine can lead to Wernicke’s encephalopathy (“WE”). If left untreated, WE can progress and become Wernicke-Korsakoff Syndrome (“WKS”). Much like a good night out, symptoms start with confusion, loss of coordination and short term memory loss. However, they progress to amnesia, then hallucinations. Some suffers incur permanent, debilitating brain damage and must be permanently institutionalized. The total cost of WKS related institutionalization is likely more than $250 million dollars per year in the US alone.[2] Patients eventually fall into a coma and die. Thankfully, treatment is relatively simple: patients just need to ensure a sufficient intake of thiamine.
You might hope that the prevalence of thiamine fortification would eliminate these conditions. And yet, up to 2.8% of all autopsies performed in the West reveal the brain lesions characteristically associated with WE.[3] Among those whose deaths were directly related to alcohol, that rate is 59%.[4] It is possible that the rate is even higher among the homeless: WE is likely underreported among this population as they are less likely to seek or receive medical treatment.
WE and the Homeless Alcoholic Population
WE is especially prevalent among the homeless and alcoholic population (the “HAP”), for three reasons. First, many alcohols, and especially strong beers, contain large amounts of calories in the form of simple carbohydrates but very low level of essential micronutrients like thiamine. Alcoholics are likely to get a significant portion of their energy requirements from alcohol and being homeless can make it extremely difficult to access enough thiamine, whether from naturally micronutrient-rich food or thiamine fortified food.[5] As such, the typical diet of an alcoholic, whether homeless or not, does not contain enough thiamine. The problem is compounded by the fact that homeless people who engage in substance abuse of any kind are much less likely to attend shelters or soup kitchens where they might get enough good food to meet their micronutrient needs. Second, the body uses thiamine to process the carbohydrates found in most alcohol. Third, alcohol itself has a negative impact on the body’s ability to process and store thiamine, so what little thiamine the patient consumes cannot be stored or utilized properly by the body.[6] [7]
Fortified Beer
The fortification of alcohol with thiamine was first seriously suggested in Australia during the 1980s. The National Health and Medical Research Council made fortification an official recommendation in 1987 but the proposal met with significant opposition from brewers and anti-alcohol groups. The Australian government decided to proceed with the fortification of flour and bread but not with beer or wine. Since the 1980s, there have not been any serious efforts to revive the proposal in Australia or elsewhere.
The Recommended Daily Allowance (“RDA”) of thiamine is 1-1.5 mg.[8] However, because of the reduced capacity of the HAP to absorb thiamine, fortification would be done through a more readily absorbed biochemical analogue, allithiamine, and levels would err on the higher side. One study suggested fortifying at a level of approximately 1mg allithiamine per 10 standard American units of alcohol.[9] It estimated the total cost of fortification[10] $11 million per year.[11] Just to remind you of the figure mentioned above: the cost of institutionalizing people with WE alone comes to $250 million dollars per year.
However, adding thiamine to all alcohols would be superfluous. The target population of homeless alcoholics are not likely to benefit from the fortification of high-end, expensive products. Therefore, we could target alcohol products which have an average retail prices of $0.50 or less per standard American unit.[12] Cheap wines, hard liquors and malt liquors would be most affected. Manufacturers could choose to fortify or to pay a levy of $0.01 per standard American unit.[13]
Sweetened Medicine and the FDA
Of course, the resulting fortified product would have to gain FDA market approval, or at least avoid censure. Asccording to the FDA’s regulatory guidance on fortification, the FDA specifically does not “not consider it appropriate to add vitamins and minerals to alcoholic beverages”.[14] Although the FDA does not directly give a reason for its position on alcohol, it may be analogized from the “jelly-bean rule”.
However, it might be argued that this specific proposal otherwise meets the FDAs regulations and guidelines for fortification.[15] The FDA strongly discourages indiscriminate fortification. Instead, the FDA recommends fortification only for “specific purposes”. The three conditions are that;
- the fortification is undertaken to correct a dietary insufficiency or to meet a demonstrated public health need;
- the fortification is rational and targeted. For example, putting calcium in soy milk for vegetarians who do not get it from dairy or putting fluoride in water to improve public dental health;
- the fortification is carried out at a level that is safe for public consumption.
It seems clear that all three conditions are met. The prevalence of WE and its cost, both in terms of money and loss of life, constitute a demonstrated public health need. The fortification is both rational and targeted: cheap alcohol is both medically effective and cost effective as a vector and will ensure that the intervention is largely confined to the target population. The demonstrated toxicity of thiamine is so low that no reasonable risk is presented by the fortification.
A Thought Experiment in Public Health and Harm Reduction
What’s the point of all this? Proof of concept for harm reduction theory. Public debate around the appropriate ways to deal with behaviors that are both considered immoral and are harmful to the health of the actor is often stultified by concerns from the “moral majority”. Not wanting to get their metaphorical hands dirty, politicians often steer clear. Objections to harm reduction interventions often take one of two forms. First, that the intervention will encourage the bad behavior.[16] However, the evidence of long-term studies on the effects of needle exchanges[17] and managed alcohol programs suggests the opposite. Second, that by acknowledging it, the government legitimizes the behavior. However, acknowledging the existence of a problem does not equate to legitimizing the problem. Rather, ignoring the problem or painting those who “cause” the problem in an indiscriminately negative light equates to the State abandoning those trapped in the cycles of substance abuse. This intervention is cheap, technically easy and could produce an incredible ROI, in terms of both money and lives saved.
[1] Vitamin B1 is also known as thiamine. Allithiamine was chosen because of its increased bioavailability.
[2] A 1978 estimated the rate of institutionalization for Korsakoff’s psychosis in the United States at 8 per million of the adult population. The figure is likely to be higher, because patients who presented with multiple conditions were not included. The total cost per year in 1978 of institutionalization alone (i.e. not including lost wages, damage to third parties caused by alcoholics, non-economic costs, etc) was estimated to be at least $70 million per year in 1978 dollars. The figure of $250 million is a conservative conversion into 2016 dollars. See, generally, Centerwall and Criqui, Prevention of the Wernicke-Korsakoff Syndrome: A Cost-Benefit Analysis New England Journal of Medicine 299(6) 285.
[3] See https://www.uptodate.com/contents/wernicke-encephalopathy#H19186644.
[4] Naidoo, Bramdev and Cooper, Autopsy prevalence of Wernicke’s encephalopathy in alcohol-related disease, South African Medical Journal 86(9) (1996) 1110.
[5] One study suggests that homeless alcoholics may get 40%-50% of their calories from alcohol. See Stefan Kertesz, Nutritional Issues, https://www.bhchp.org/sites/default/files/BHCHPManual/pdf_files/Part3_PDF/Nutritional_Issues.pdf.
[6] Anastacio Hoyumpa, Alcohol and Thiamine Metabolism, Alcoholism: Clinical and Experimental Research 7(1) (1983) 11.
[7] ibid.
[8] See https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/#h2.
[9] This figure is based on the definition of an alcoholic as someone who consumes at least 0.5 liters of hard liquor, 2 liters of wine or 4 liters of beer per day. It was noted that, given an RDA of 1.5 mg, adding 2 mg of allithiamine to every 0.5 liters of spirits, 2 liters of wine and 4 liters of beer would be sufficient to alleviate the deficiency. Centerwall and Criqui, Prevention of the Wernicke-Korsakoff Syndrome: A Cost-Benefit Analysis New England Journal of Medicine 299(6) 285.
[10] Cost of allithiamine plus extra cost of manufacturing.
[11] In 2016 dollars. The figure from the original study was $3 million.
[12] See Appendix 1 for a series of example calculations.
[13] A 1978 study estimated that if the total cost of fortification were passed on to the consumer, the price of wine would rise by $0.003 per standard American unit (converted to 2016 dollars). Manufacturers are unlikely to have any qualms about passing this on to the consumer. But the initial incorporation of fortification into the production process is likely to be disruptive. Therefore, the levy must be high enough that manufacturers would prefer to pass the cost of fortification, rather than the levy, onto the consumer. See Centerwall and Criqui, Prevention of the Wernicke-Korsakoff Syndrome: A Cost-Benefit Analysis New England Journal of Medicine 299(6) 285.
[14] Guidance for Industry: Questions and Answers on FDA’s Fortification Policy¸ FDA (November 2015), https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm470756.htm
[15] Guidance for Industry: Questions and Answers on FDA’s Fortification Policy¸ FDA (November 2015), :.
[16] See, for example, https://hepcproject.typepad.com/hep_c_project/2004/05/congressional_a.html
[17] WHO, Effectiveness of Sterile Needle and Syringe Programming in Reducing HIV/AIDS Among Injecting Drug Users, (2004), https://www.who.int/hiv/pub/prev_care/effectivenesssterileneedle.pdf.
