I am APOE4/4 and blessed with LP(a). I buried my parents, brother, two aunts, three grandparents who died from dementia/Alzheimers. More remote relatives have also passed from the disease. I started have mild memory issues recently. I read Nick’s Substack and others on YouTube on lithium. I started 3mg of lithium ororate and few months ago and saw immediate benefits including better recall of numbers, passwords, clarity of vision, recall of read material and calmer emotions. Just increased to 5mg as an experiment with only minor improvement. I will drop back to 3mm next month unless I see more benefit. No side effects noticed. I worry about weight gain as I am trying to lose my recent 15lb gain and I seem to have stalled.
I also carry the Lp(a) gene, with levels in the ~50 mg/dL range. I’m truly sorry to hear you’ve lost so many family members.
Have you looked into NMN (NAD precursor) supplementation? Nick shared an interesting post on it recently that you might find useful. As for Lithium, weight gain is primarily associated with high-dose therapeutic levels. At very low doses (5–10 mg), if weight changes occur, they’re more likely related to appetite effects rather than lithium itself. I don’t see convincing evidence that low-dose lithium causes weight gain.
Thanks Karin, I am confused a bit after reading Nick’s article on Ezetimibe. I was prescribed Ezetimibe a year ago January. My doctor told me that I needed to lower my LDL to below 65 if I wanted to see a reduction of the calcified plaque which increased after my 2020 stroke level of 30 to 100 January 2025. Like Nick, I had bad diarrhea and stopped after a month. I started Ezetimibe again in the morning with no issues. I take Magnesium at night. After his Lithium article, I added Lithium and saw significant improvements. No I am not sure either the improvement came from Ezetimibe, lithium or both. I will stick with both for now and tease it out later.
Thank you Karin. I share the same sentiment expressed by James. I too have been taking Lithium orotate for the past 2 years after reading the data and following you as well as Nick’s Substack. The past year I increased the dose to 10 mgs.
Thanks Karin for another remarkable and enlightening article. You are a real source of wisdom and insight and thank you for all you do. Anecdotally, many people/patients I know who have one or two apo E4 alleles are unusually intelligent. The APOE4 allele likely conferred survival advantages in ancient environments—perhaps by aiding fat metabolism or bolstering immune defenses. But, in today’s calorie-rich, longer-living context, it heightens Alzheimer’s risk—likely because of effects on lipid metabolism, inflammation, and energy use in the brain. Regardless of its origins, Karin, you are a genius – level intellect and are making important contributions that will likely powerfully reduce the risk for AD, especially for those of us positive for APO E4. All this to say, Lithium seems to be working in your N=1 experiment. Have you notice any side effects from lithium orotate?
Thank you, James, I really appreciate your kind words. As I was preparing the article, I pulled out an old Toxic & Essential Elements hair analysis from 2019, well before I ever began supplementing with lithium. Interestingly, the only mineral that was off-the-charts high was Lithium: 0.085 µg/g (reference range 0.007–0.020 µg/g). I suspect this reflects lifelong exposure from well water, as I’ve lived on acreage properties since my early 30s, where trace mineral content is often higher. That result has made me wonder whether long-term, low-level environmental Lithium exposure could have been quietly neuroprotective - particularly for my APOE4/4 brain. It also raises a another question: Alzheimer’s incidence rose sharply in the 20th century, roughly coincident with the widespread adoption of centralized water treatment and municipal water systems. Whether that overlap is meaningful or purely coincidental is unknown, but it’s a question worth asking rather than dismissing outright. To your question: no, since supplementing with low-dose lithium, I haven’t noticed any side effects.
That correlation doesn’t hold at environmental or low doses which we are talking about here. Population data generally show the opposite. Weight gain is mainly seen with high-dose psychiatric lithium and is often indirect, not metabolic obesity. Context matters.
Biology isn’t that linear. I had lithium levels ~3× population reference long before adding supplementation and have remained lean. That’s why blanket claims like this don’t persuade me. If there’s an effect, it’s more likely appetite-mediated in a subset of people at prescription doses - definitely not a universal, dose-independent obesity effect. Even if weight gain were a risk, I’d take that over dementia every time.
I am APOE4/4 and blessed with LP(a). I buried my parents, brother, two aunts, three grandparents who died from dementia/Alzheimers. More remote relatives have also passed from the disease. I started have mild memory issues recently. I read Nick’s Substack and others on YouTube on lithium. I started 3mg of lithium ororate and few months ago and saw immediate benefits including better recall of numbers, passwords, clarity of vision, recall of read material and calmer emotions. Just increased to 5mg as an experiment with only minor improvement. I will drop back to 3mm next month unless I see more benefit. No side effects noticed. I worry about weight gain as I am trying to lose my recent 15lb gain and I seem to have stalled.
I also carry the Lp(a) gene, with levels in the ~50 mg/dL range. I’m truly sorry to hear you’ve lost so many family members.
Have you looked into NMN (NAD precursor) supplementation? Nick shared an interesting post on it recently that you might find useful. As for Lithium, weight gain is primarily associated with high-dose therapeutic levels. At very low doses (5–10 mg), if weight changes occur, they’re more likely related to appetite effects rather than lithium itself. I don’t see convincing evidence that low-dose lithium causes weight gain.
Thanks Karin, I am confused a bit after reading Nick’s article on Ezetimibe. I was prescribed Ezetimibe a year ago January. My doctor told me that I needed to lower my LDL to below 65 if I wanted to see a reduction of the calcified plaque which increased after my 2020 stroke level of 30 to 100 January 2025. Like Nick, I had bad diarrhea and stopped after a month. I started Ezetimibe again in the morning with no issues. I take Magnesium at night. After his Lithium article, I added Lithium and saw significant improvements. No I am not sure either the improvement came from Ezetimibe, lithium or both. I will stick with both for now and tease it out later.
Thank you Karin. I share the same sentiment expressed by James. I too have been taking Lithium orotate for the past 2 years after reading the data and following you as well as Nick’s Substack. The past year I increased the dose to 10 mgs.
Thanks Karin for another remarkable and enlightening article. You are a real source of wisdom and insight and thank you for all you do. Anecdotally, many people/patients I know who have one or two apo E4 alleles are unusually intelligent. The APOE4 allele likely conferred survival advantages in ancient environments—perhaps by aiding fat metabolism or bolstering immune defenses. But, in today’s calorie-rich, longer-living context, it heightens Alzheimer’s risk—likely because of effects on lipid metabolism, inflammation, and energy use in the brain. Regardless of its origins, Karin, you are a genius – level intellect and are making important contributions that will likely powerfully reduce the risk for AD, especially for those of us positive for APO E4. All this to say, Lithium seems to be working in your N=1 experiment. Have you notice any side effects from lithium orotate?
Thank you, James, I really appreciate your kind words. As I was preparing the article, I pulled out an old Toxic & Essential Elements hair analysis from 2019, well before I ever began supplementing with lithium. Interestingly, the only mineral that was off-the-charts high was Lithium: 0.085 µg/g (reference range 0.007–0.020 µg/g). I suspect this reflects lifelong exposure from well water, as I’ve lived on acreage properties since my early 30s, where trace mineral content is often higher. That result has made me wonder whether long-term, low-level environmental Lithium exposure could have been quietly neuroprotective - particularly for my APOE4/4 brain. It also raises a another question: Alzheimer’s incidence rose sharply in the 20th century, roughly coincident with the widespread adoption of centralized water treatment and municipal water systems. Whether that overlap is meaningful or purely coincidental is unknown, but it’s a question worth asking rather than dismissing outright. To your question: no, since supplementing with low-dose lithium, I haven’t noticed any side effects.
That correlation doesn’t hold at environmental or low doses which we are talking about here. Population data generally show the opposite. Weight gain is mainly seen with high-dose psychiatric lithium and is often indirect, not metabolic obesity. Context matters.
Biology isn’t that linear. I had lithium levels ~3× population reference long before adding supplementation and have remained lean. That’s why blanket claims like this don’t persuade me. If there’s an effect, it’s more likely appetite-mediated in a subset of people at prescription doses - definitely not a universal, dose-independent obesity effect. Even if weight gain were a risk, I’d take that over dementia every time.